mt_monashmedfandomcom-20200213-history
L0301P18 - Lipid Metabolism
__TOC__ Lipids Triacylglycerols *3 fatty acids + glycerol *primary energy storage in mammals *major dietary source of lipids Phospholipids *2 fatty acid + 1 or more phosphate groups *contained in membranes Sterols *e.g. cholesterol *precursors for bile acids, steroid hormones and vitamin D *contained in membranes Fatty Acids *saturated fatty acids - no double bonds *unsaturated fatty acids **one or more double bond **monounsaturated or polyunsaturated Fatty Acid Synthesis *complex endergonic process *primarily occurs in the liver **although it occurs in a variety of tissues *occurs when there is excess energy *regulated by nutritional status *high carbohydrate/low fat diet = faster rate *starvation/fasting or high fat diet - slower *tightly regulated process: **activated by insulin = excess glucose **inhibited by glucagon and epinephrine First Committed Step *bicarbonate + acetyl-CoA —> malonyl-CoA *uses ATP (1/cycle) and NADPH (2/cycle) *enzyme - acetyl-CoA carboxylase (ACC) *cofactor - biotin (B group vitamin) Example #8 Acetyl CoA + 7ATP +14NADPH—> Malonyl CoA #cyclical process:  #*Malonyl CoA added into 2-C increments to fatty acid chain until its 16 carbons long = Palmitoyl CoA (to form palmitate or be used to synthesis longer fatty acid chains) #can be converted into triglycerides etc Buildup of Palmitoyl CoA *will act in a negative feedback loop and inhibit the action of Acetyl CoA Carboxylase Triacylglycerol (TAG) Synthesis *occurs in both the liver and adipose cells from different precursors *Glycerol 3 phosphate is the backbone (main precursor) to form TAG Process: In the liver #Glycerol is phosphorylated into glycerol 3 phosphate by glycerol kinase #2 fatty acids (acyl CoA) added onto the Gly3P to form phosphatidic acid #Add a phosphate to form a diacylglycerol #Phosphate group cleaved off so the 3rd fatty acid chain is added to form the TAG #TAG either enters blood in very low density lipoproteins (VLDL) or stays in the liver Process: In adipose cells *Only occurs when there is excess glucose/ glycolysis is occurring as they do not contain glycerol kinase (so glycerol cannot be used) #Glucose forms dihydroxyacetone phosphate via glycolysis (as it is an intermediate) #Converted to Gly3P #Then same pathway as liver (s.2 onwards) #TAG is stored in the adipose cells Phospholipid Synthesis *similar to TAG synthesis *occurs in all animal cells except RBC Process #Same steps as TAG synthesis to produce phosphotidate (phosphatidic acid) #A head group is added to phosphotidate to form the phospholipid #*head group includes serine, choline and ethanol amine Ketone Bodies *occurs in liver cells - hepatocytes *made from: **carbon skeletons are from amino acids **acetyl CoA from breakdown of fatty acids *three types: **acetone **acetoacetate **β-hydroxybutyrate *occurs when tissues need extra energy but only small amounts produced unless severe starvation or untreated diabetes *energy source for heart, skeletal muscle, kidney of brain Cholesterol *hydrophobic 4 carbon ringed molecule *majority of cholesterol in blood stream in esterified to fatty acids (i.e. fatty acid attached to the OH on cholesterol) *generally no immediate need for it *cannot be digested in the GIT or metabolised in mammalian cells *removal: **via transfer into GIT and excreted **~50% by conversion to bile acids **reduced by bacteria and excreted *normal conditions - balance between losses through faecal excretion and absorption and de novo synthesis Functions *essential component in cell membranes **maintains membrane fluidity *precursor for: **bile acids - digestion and absorption of fats in the gastrointestinal tracts **steroid hormones **vitamin D Source *from diet **~70% ingested cholesterol is absorbed *synthesised mainly in the liver, but also the adrenal cortex and gonads Synthesis *formed from acetyl CoA *multistep process *enzyme: HMG-CoA reductase **highly regulated **some drugs target this enzyme **inhibited: ***high intracellular cholesterol levels ***glucagon increase (not enough energy) **stimulated: ***low intracellular cholesterol levels ***insulin increase (lots of energy)  Serum Albumin *protein involved in the release of fatty acids from adipocytes Process #hormones adrenaline and glucagon trigger mobilisation of fatty acids from adipose cells #triacylglycerol lipase cleaves TAG into fatty acids and glycerol #fatty acids diffuse out of cell and bind to albumin in blood #fatty acids dissociate from albumin and enter cytosol of cells Lipoproteins *transports fats and cholesterol from the liver or GIT around the body Structure *Core: **hydrophobic **insoluble lipid, TAG and cholesterol esters *External Coat: **polar **phospholipid monolayer, free cholesterol and apoproteins Apoproteins *also known as apolipoproteins *small proteins on the external surface of lipoproteins embedded in the phospholipids *differentiate each type of lipoproteins *carry specific receptors for receptor mediated endocytosis *provide structural stability *act as cofactors that inhibit or activate enzymes acting on lipids *can be transferred between lipoproteins Major Types of Lipoproteins Chylomicron *88% TAG - highest *synthesised in intestinal cells after meals *carries dietary TAG and cholesterol from intestines to body tissue *makes blood plasma appear cloudy *after release TAG (enzyme: lipoprotein lipase), chylomicron converted to chylomicron remnants *chylomicron remnants are taken up by liver cells and removed after use VLDL *very low density lipoproteins (56% TAG) *synthesised in the liver *carries liver produced TAG from liver to body cells in between meals *after release of TAG, become VLDL remnants (also known as IDL) then either taken up liver cells or converted to LDL LDL *low density lipoprotein *chief carrier of cholesterol **58% cholesterol *carries cholesterol to body tissue (especially adrenal glands) and liver *long life time in the blood **is known as bad cholesterol and may cause atherosclerosis *taken up by the liver by receptor-mediated endocytosis to be recycled HDL *high density lipoprotein *made predominantly in the liver *maintains serum cholesterol levels and prevents blocked arteries **is known as good cholesterol *don’t contain much when released from liver *reverse cholesterol transport **collects and carries cholesterol away from body tissues to the liver in the form of cholesterol esters